Porous synthetic vascular grafts with oriented ingrowth channels

ABSTRACT

A vascular prosthesis is constructed from a structure having interconnected, helically oriented channel-porosity to allow oriented ingrowth of connective tissue into a wall of the prosthesis. The prosthesis can have a small internal diameter of 6 mm or less. Several different methods can be used to produce the prosthesis, including a fiber winding and extraction technique, a melt extrusion technique, and a particle and fiber extraction technique using either a layered method or a continuous method. Furthermore, mechanical properties of the prosthesis are matched with mechanical properties of the host vessel, thereby overcoming problems of compliance mismatch.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of application U.S. Ser. No. 10/187,522filed Jul. 2, 2002 entitled “Porous Synthetic Vascular Grafts withOriented Ingrowth Channels,” which is a continuation of application U.S.Ser. No. 09/434,071 filed Nov. 5, 1999 entitled “Porous SyntheticVascular Grafts with Oriented Ingrowth Channels,” which issued as U.S.Pat. No. 6,540,780 on Apr. 1, 2003, and which claimed the benefit ofprovisional application U.S. Ser. No. 60/109,526 filed Nov. 23, 1998entitled “Small Diameter Vascular Prosthesis,” all of which areincorporated herein by reference.

FIELD OF THE INVENTION

This invention is directed to a vascular prosthesis having orientedchannel-porosity to allow for oriented ingrowth of connective tissueinto a wall of the prosthesis. Furthermore, mechanical properties of theprosthesis are matched with mechanical properties of a host vessel,thereby overcoming problems of compliance mismatch.

BACKGROUND OF THE INVENTION

Vascular disease in small to medium diameter arteries adversely affectsarterial wall structure. As a result, blood flow through the vessel ishindered either by total occlusion or, in the opposite extreme, an acuteover dilation of the vessel (aneurysm). Such indications usually requirereconstructive or bypass surgery. The most successful replacements atpresent are autologous grafts (arteries and veins taken from the host),but often these are too diseased or unsuitable for use as an implant.There is thus a great need for the development of a reliable smalldiameter vascular prosthesis.

Over the last 40 years, considerable progress has been made in thedevelopment of arterial prostheses. The modern era of vascular surgerybegan in the early 1950's, 40 years after Carrel and Gutherie (1906)demonstrated that autologous veins could be used to replace arteries.With the advent of antibiotics and anticoagulants in ancillary medicine,the development of vascular prostheses prospered. The reversed saphenousvein was soon considered the best artery replacement and was usedsuccessfully in femoral artery replacement by Kunlin in 1949. However,the need for a smaller prosthesis led to further research by Gross andassociates involving homografts using sterilized tissue. Although earlyresults were encouraging, the long-term results were stillunsatisfactory, with the grafts often failing due to thrombosis andaneurysm.

While pioneers such as Gross et al. (1948) continued to work on hetero-and homografts, Voorhees made an important observation in 1952 thatchanged the direction of vascular prosthetic development. Afterdiscovering that cells grew on silk thread exposed to blood, he showedthe effectiveness of synthetic textile or fabric tubes as arterialreplacements. A new era of vascular surgery began and the search for themost suitable material and optimal structure for a textile graft began.Experiments, even recently, have investigated factors such as knitted orwoven textiles, large or small pores, different surface finishes andcrimping and external reinforcing.

Presently, the materials used for vascular implants are tanned naturalvessels, textile tubes made from woven or knitted Dacron, or tubes madefrom expanded polytetrafluoroethylene (e-PTFE). These grafts aresuccessful for large diameter artery replacement where there is a highblood flow rate; but they have a much lower success rate in arterieswith a diameter less than 6 mm. These conventional prosthetic vasculargrafts do not permit unrestricted vessel ingrowth from the surroundingtissue due mostly to ingrowth spaces that are either too narrow ordiscontinuous. All of the present grafts eventually fail by occlusiondue to thrombosis (fibrous tissue build up), or intimal hyperplasia(exuberant muscle growth at the interface between artery and graft).

Factors such as the thrombogenic nature of the graft material, surfaceroughness, the mechanical and hemodynamic properties of the graft andthe condition of the host artery are known to influence the success ofthe graft. Although the reasons for failure are not fully understood, itis largely agreed that compliance mismatch between artery and graft isthe predominant issue surrounding the failure of small diameterprostheses. Discontinuity in mechanical properties between the graft andartery alters the blood flow resulting in a fibrous tissue build-upleading to the complete occlusion and hence failure of the graft.

One of the main reasons for a fibrous build up on the graft is thethrombogenic reaction of the blood with the graft material. Much of thecurrent research involves the development of various polymers,especially polyurethanes, to which biological coatings can be applied toimprove the stability of the graft in the body over long periods.Ideally the graft should have an endothelial cell lining on the innerwall. This prevents a reaction by providing a less thrombogenic flowsurface for the blood passing through it. One way of achieving this isthrough a porous graft structure. This, in conjunction with suitablebiological engineering, can induce cell ingrowth through the wallleading to musculogenesis and the eventual endothelialization of theinner surface.

Autologous grafts, such as the saphenous vein and the internal mammaryartery are still considered the best grafts for the reconstruction ofsmall peripheral arteries, but these are often too diseased orunsuitable for use as a graft. None of the present textile grafts(e-PTFE and Dacron) have proved successful for long periods. Manyapproaches to graft production have been developed in an effort tocreate a porous polyurethane artery graft. Indeed, it has been shownthat it is possible to create an initially compliant porous graft.However, the long-term success of such grafts remains to be proven. Ithas become apparent that the current methods of graft construction areineffectual and a new approach is necessary.

It is evident that the present small diameter grafts do not provide anacceptable long-term patency. Although the causes for failure are notimmediately clear, it is apparent that none of the previous prostheseshave the same structure as an artery or behave mechanically as an arterydoes. Apart from the biological issues, which are arguably the mostimportant and complex issues in graft design, one of the central issuesinvolves understanding the mechanics of arterial behavior. Recentinvestigations have addressed the issue of compliance in an effort tocreate a structurally similar graft, but compliance alone has not provedcompletely successful. Thus, there is a need to develop a graft thataddresses the issue of mechanical behavior through structure. The graftstructure should create an optimal strain environment that willfacilitate and encourage the development and maintenance of endothelialand smooth muscle cells in the vessel.

SUMMARY OF THE INVENTION

The present invention is directed to a synthetic vascular graft withhelically oriented, interconnected transmural ingrowth channels.Vascular tissues are mostly helically arranged in the walls of naturalarteries. This invention allows for helically oriented ingrowth ofconnective tissue into walls of synthetic graft prostheses in order tosimulate mechanical properties of natural vessels.

Several different methods can be used to produce the graft of thepresent invention. In one method, a tube is fashioned from a graftmaterial by coating an extractable fiber with a solution containing abiocompatible material including the graft material, and then windingthe fiber onto a mandrel in a winding device. Precipitation of thesolution and extraction of the fiber renders a tubular structurecontaining helically oriented, interconnected transmural ingrowthchannels in the tube wall suitable for use as a synthetic,small-diameter vascular graft prosthesis.

In another method, a paste comprising a polymer solution and anextractable filler is prepared and deposited in a layer onto a mandrel.An extractable fiber is also wound onto the mandrel. The paste and fibercan be applied to the mandrel either simultaneously or successivelyalternating between the paste and the fiber, until a desired thicknessof the graft is achieved. Precipitation of the solution and extractionof the fiber produces the graft of the invention.

An alternative method for making the invention involves melt extrusionof a polymer containing strands of soluble fiber, with or withoutphysically or chemically blowing a foamed tube.

With the foregoing in mind, it is a feature and advantage of theinvention to provide a synthetic vascular graft wherein mechanicalproperties of the graft are matched with mechanical properties of thehost vessel, thereby overcoming problems of compliance mismatch.

It is another feature and advantage of the invention to provide asynthetic vascular graft that contains helically oriented,interconnecting, transmural ingrowth channels.

It is a further feature and advantage of the invention to provide amethod for producing a synthetic vascular graft that contains helicallyoriented, interconnecting, transmural ingrowth channels.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic drawing of a preferred method of producing thesynthetic vascular graft of the invention.

FIG. 2 is a schematic drawing of an alternate method of producing thesynthetic vascular graft of the invention.

FIGS. 3 a-3 f are a series of perspective views of a mandrel from FIG. 2as the method is carried out.

DEFINITIONS

The term “extractable fiber” means any polymeric or other fiber materialthat is soluble and extractable by a solvent other than the solvent usedfor the graft material. The fiber has a diameter ranging in size from 10to 300 micrometers, more preferably from 40 to 110 micrometers. Thestandard deviation of fibers used in this invention is typically lessthan 20 micrometers, more preferably less than 10 micrometers. Examplesof suitable materials include alginate, gelatin, carbohydrates (sugar,dextrose, etc.), inorganic and organic salts. Water soluble fibers aresuitable when water is the precipitation solvent and the fiberextractor.

The term “fiber extraction solvent” means any solvent capable ofdissolving the extractable fiber without adversely affecting the graftstructure. For example, water is a suitable fiber extraction solvent forwater soluble fibers.

The term “non-extractable fiber” means any polymeric or other fibermaterial that is not extractable by the fiber extraction solvent. Thefiber is either elastic or non-elastic non-degradable material, or acombination of elastic and non-elastic materials. Additionally, areinforcing material that is either elastic or non-elastic, and isdegradable in vivo, can be used in combination with the non-degradablematerial to provide initial strength to the graft. The non-extractablefiber typically has a diameter ranging in size from 10 to 100micrometers. Examples of suitable non-elastic, non-degradable materialsinclude polyethylene terephthalate (PET, Dacron) andpolytetrafluoroethylene (PTFE). Examples of suitable elasticnon-degradable materials include thermoplastic polyurethanes, e.g. M48,Pellethane (or clones), Biomer (or clones), or any other biocompatibleelastomer. Degradable polyurethanes can serve as degradable reinforcingfibers.

The term “precipitation solvent” means any solvent that is capable ofprecipitating the graft material from solution. The precipitationsolvent and the graft material solvent are usually miscible in allproportions. Examples of suitable precipitation solvents include: water,ethanol, acetone, or combinations of any of these. The fiber extractionsolvent and the precipitation solvent may or may not be the samesolvent.

The term “graft material” means any polymeric or other material that canbe dissolved in a suitable solvent and re-solidified after graftmanufacture by air-drying, phase inversion, or combinations thereof.Examples of suitable graft materials include: thermoplastic elastomersincluding thermoplastic polyurethanes, e.g. Pellethane, Biomer typepolyurethanes, Chronoflex, and Hydrothane. In particular, a polyurethanedeveloped by Medtronic and described in U.S. Pat. No. 4,873,308 is anexample of a suitable graft material.

The term “graft material solvent” means any solvent capable ofdissolving the graft material. Examples of suitable solvents forpolyurethanes include: N-methylpyrrolidone (NMP), N,N dimethyldiacetamide (DMAC), 1,4 dioxane, etc.

The term “graft material solution” means a solution of the graftmaterial in the graft material solvent in concentrations ranging from 1to 40% by mass, more typically 5 to 30% by mass, usually 10 to 25% bymass.

The term “graft material paste” means an admixture consisting of a graftmaterial solution and an extractable filler. The ratio of filler topolymer in the solution can range from 20:1 to 1:1, more typically from10:1 to 5:1 (ratios by mass).

The term “chemical blowing agent” means any material that decomposes toform a gas, e.g. CO₂ or N₂, wherein the gas creates pores in the graftmaterial. Examples of chemical blowing agents include sodium bicarbonateand azodicarbonamides.

The term “physical blowing agent” means either a liquid or a gas that isintroduced to molten graft material under pressure, wherein evaporationof the liquid or expansion of the gas creates bubbles that form pores inthe graft material. Examples of physical blowing agents include:chloro-fluoro carbons (e.g. freon), pentane, and hexane.

The term “extractable filler” means any polymeric or other fillermaterial that is soluble and/or extractable by a solvent other than thesolvent used for the graft material. The material is preferablyspherical in shape with average diameters ranging in size from 10 to 300micrometers, more preferably from 40 to 110 micrometers. The standarddeviation of the diameters of the pores is typically less than 20micrometers, more preferably less than 10 micrometers. Examples ofsuitable materials include protein beads, e.g. alginate, gelatin,carbohydrates (sugar, dextrose, etc.), inorganic and organic salts.Water soluble fillers are suitable when water is the precipitationsolvent and the filler extractor.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

This invention is directed to an improved prosthetic vascular grafthaving a synthetic scaffold of transmural ingrowth channels which arecharacterized by an interconnected, helical orientation. A process ofproducing such channels in a synthetic scaffold can be achieved using anextractable fiber. The product and process are explained in detailbelow.

In order to promote ingrowth of connective tissue, it is important thatmechanical properties of the graft are closely matched with mechanicalproperties of a host vessel, thereby overcoming problems of compliancemismatch. Although structure of blood vessels varies through a body, a“typical” artery consists of three distinct layers, each performingspecific basic functions. An intima, consisting of an endotheliumattached to a basement membrane, provides a non-thrombogenic bloodcontacting surface. A media contains smooth muscle cells (SMC's) as wellas elastic and other intercellular connective and matrix materials, andsupplies two other important properties to a blood vessel, namelycompliance and contractility. In order to achieve these properties,tissues are oriented in a helical fashion in this medial layer. Anotherimportant property, namely structural integrity, is provided by anadventitia. A configuration of collagen fibers in the adventitiaprovides for “stiffening” of the vessel when subjected to high internalpressures, i.e. a decrease in compliance with increased strain.

The graft of the present invention has helically oriented,interconnected, transmural ingrowth channels that correspond to thehelical arrangement of vascular tissues in the walls of naturalarteries. The graft structure thereby creates an optimal strainenvironment that facilitates and encourages the development andmaintenance of endothelial and smooth muscle cells in the vessel. Bygetting the smooth muscle cells to grow helically on the graft along thespiral channels, the graft acquires radial compliance and behaves like areal blood vessel. To achieve high porosity, the channels should bearranged at a very narrow angle, for example a 200 micron pitch. Forlarger wind angles, for example a 10 mm pitch, multiple fibers, all thesame or a combination of soluble and reinforcing, can be wound aroundthe graft to form corresponding channels. The pitch can be variedthrough the thickness of the wall by increasing or decreasing the pitchat a predefined rate as one builds up the graft wall, or alternatingbetween two or more pitches in alternate layers. Preferably, thechannels have diameters in a range of 10-300 μm, more preferably in arange of 40-110 μm.

In designing the vascular prosthesis of the invention to result information of a neo-artery mimicking the properties of a natural vessel,material for the scaffold should have biostability, processability,availability, and desirable mechanical properties. The porous scaffoldshould provide high porosity for maximal cell ingrowth and minimal bulkcompressibility (to allow for compressibility associated withcontractility). The prosthesis should have structural integrity andviscoelastic properties similar to those observed for natural vessels.Furthermore, in order to minimize foreign body reaction and to encouragedifferential cell ingrowth, the scaffold materials should also exhibitlong-term in-vivo stability. Examples of suitable scaffold materialsinclude thermoplastic elastomers, particularly thermoplasticpolyurethanes.

Because of their unique combination of physical, chemical andbiocompatible properties, polyurethanes are preferred for use as theprimary scaffold material in the vascular graft of the invention.Enzymatic hydrolysis, auto-oxidation, mineralization, and biologicallyinduced environmental stress cracking of polyester- andpolyetherurethanes have led manufacturers of medical polyurethanes todevelop more specialized formulations to prevent these occurrences.Examples of particularly suitable medical polyurethanes includePellethane, Biomer type polyurethanes, Chronoflex, and Hydrothane.

Helical channels are formed in the vascular graft by winding anextractable fiber into the graft material before the graft is set.Fibers suitable for forming the channels include alginate, gelatin,carbohydrates, inorganic and organic salts. Selection of a suitablefiber material to create the channels requires careful consideration.The fibers can be round, flattened round, or elliptical. A flattenedround fiber provides superior interconnectivity, but can be difficult towind.

A multifactorial method (phase inversion/precipitation) can be used tosolidify the scaffold material around the fibers. The solutionproperties of the fiber material are vital parameters in the processbecause the fiber material must be able to be solidified within thescaffold material and then extracted with a solvent while the scaffoldmaterial remains intact. The extractable fiber material should benon-soluble in the solvent used to dissolve the scaffold material,readily soluble in the precipitation solution, processable into fibers,and non-toxic. Furthermore, the fiber material should have sufficientmelt strength to be drawn down to desired dimensions (within about ±10μm of the desired dimensions) and be strong enough in the fiber form towithstand winding. An additional, non-extractable fiber can be used inthe graft of the invention to provide structural reinforcement.

The vascular graft of the present invention can be achieved by forminginterconnecting, helically oriented channels in a wall of an elastomericpolymeric tubular structure using extractable fibers to form thechannels. Suitable extractable fibers include those made from alginate,gelatin, carbohydrates, inorganic and organic salts. The fibers shouldhave diameters of 10 to 300 micrometers, more preferably 40 to 110micrometers. Several different methods can be used to produce thesegrafts.

The most preferred method for producing the graft of the presentinvention is a fiber winding and extraction technique. This method isillustrated in FIG. 1. The method involves assembling a mandrel 12 in acustom-designed winding device 10. The device 10 can be as simple as apersonal computer 11 attached to a controller 13 which is furtherattached to two motors 15 and 17. One motor 15 drives translationalmovement of the fiber 14, while the other motor 17 drives rotation ofthe mandrel 12. The device 10 allows for accurate control over windingspeed and position of the rotating mandrel 12 and translational movementof the fiber 14, thereby allowing for the accurate placement of woundfibers on the mandrel 12. The mandrel 12 has a diameter corresponding toa desired internal diameter of a resulting graft. The internal diameterof the graft is preferably between 1 mm and 20 mm, more preferably inthe range of 2 to 6 mm for small diameter vessel replacement.

Once the winding device 10 is assembled, an extractable fiber 14 iscoated with a solution 18 containing a biocompatible material. Theextractable fiber 14 is made of alginate, gelatin, carbohydrates, orother soluble polymers, for example. The coating solution 18 includes asuitable graft material dissolved in a suitable graft material solvent.The coating solution may additionally contain soluble particulatefillers, such as microbeads, allowing for the creation of both sphericaland channel-like porosity in the same graft. Suitable graft materialsinclude thermoplastic elastomers, particularly thermoplasticpolyurethanes, such as Pellethane, Biomer type polyurethanes,Chronoflex, Hydrothane, Estane, Elast-Eon, Texin, Surethane, Corethane,Carbothane, Techoflex, Tecothane and Biospan. Suitable graft materialsolvents for polyurethanes include N-methylpyrrolidone (NMP), N,Ndimethyl diacetamide (DMAC), 1,4 dioxane, etc. Concentration of thegraft material in the graft material solvent ranges from 1 to 40% bymass, more typically 5 to 30% by mass, usually 10 to 25% by mass. Theconcentration depends on various factors, including composition of thegraft material, composition of the graft material solvent, and viscosityof the solution. After the fiber 14 is coated, the fiber 14 is woundonto the mandrel 12.

An additional non-extractable fiber 16 can also be wound onto themandrel 12 for reinforcement. The non-extractable fiber 16 can be eitherelastic or non-elastic, or a combination of elastic and non-elasticmaterials. Additionally, a reinforcing material that is either elasticor non-elastic, and is degradable in vivo, can be used in combinationwith the non-degradable material to provide initial strength to thegraft. The reinforcement material that is degradable in vivo degrades asthe graft is populated by ingrowing cells and accompanying extracellularmatrix material. Ingrowing material tends to stiffen the graft;therefore, a degradable fiber can be used to give initial strength tothe graft without making the graft overly stiff after ingrowth. Thenon-extractable fiber 16 typically has a diameter ranging in size from10 to 100 micrometers. Examples of suitable non-elastic non-degradablematerials include polyethylene terephthalate (PET, Dacron) andpolytetrafluoroethylene (PTFE). Examples of suitable elastic,non-degradable materials include thermoplastic polyurethanes, e.g. M48,Pellethane (or clones), Biomer (or clones), or any other biocompatibleelastomer. Degradable polyurethanes can serve as degradable reinforcingfibers 16.

Tension on the extractable fibers 14 ensures “touching” of intersectingfiber strands, thereby ensuring communication between helical channelswhen the fibers 14 are extracted. The coating solution 18 is thensolidified by phase precipitation, wherein the graft is immersed into aprecipitation solvent, and/or by drying. Examples of suitableprecipitation solvents include water, ethanol, acetone, or combinationsof any of these. The extractable fiber 14 is extracted by applying afiber extraction solvent to produce channels in the space occupied bythe fiber 14.

Another method for producing the graft of the invention is a meltextrusion technique with oriented fibers. In this method, a molten graftmaterial containing chopped strands of extractable fibers is extrudedfrom an extrusion die specially adapted to orient fibrous fillers in anextrudate. The extrusion results in a tubular structure having aninternal diameter preferably between 1 mm and 20 mm, more preferably ina range of 2 to 6 mm for small diameter vessel replacement. The graftmaterial can also contain additional, non-extractable fibers forreinforcement. Physical and/or chemical blowing agents can be used toproduce a foamed graft. In addition to choosing a suitable blowingagent, extrusion conditions must also be chosen carefully in order toavoid such obstacles as skin formation. There are various types ofpost-treatment for converting closed cell foams to open cell foams,which essentially entails removing a thin membrane between the cells orpores. One method involves heat treatment. By treating the closed cellfoam in a controlled, elevated temperature environment, it is possibleto melt the thin membrane without melting the rest of the material. Thetemperature depends on the graft material. Another method for convertingclosed cell foams to open cell foams is a mechanical method. By crushingthe closed cell foam between rollers or a similar device, the thinmembrane will rupture due to the pressure in the pore. A third method isanother mechanical method wherein explosive gasses (e.g. stoichiometricratios of O₂/H₂) are infiltrated into the pores. The cells are rupturedby ignition of these gasses. Yet another method is a chemical methodwhereby the foam is subjected to hydrolysis, thereby destroying thethinner membranes more rapidly than the thicker ribs defining the pores.Any of these methods can be used alone or in combination to produce opencell foams.

Yet another method for producing the graft of the invention is aparticle and fiber extraction technique using a layered method. Thismethod is illustrated in FIGS. 2 and 3 a-3 f. In this method, a paste 30is prepared from a graft material solution and an extractable filler,wherein the graft material solution comprises a graft material and agraft material solvent. As in the coating solution of the fiber windingand extraction technique, the suitable graft materials includethermoplastic elastomers, particularly thermoplastic polyurethanes, suchas Pellethane, Biomer type polyurethanes, Chronoflex, and Hydrothane;and suitable graft material solvents include N-methylpyrrolidone (NMP)and 1-methyl-2-pyrrolidinone. Suitable materials for the extractablefiller include protein beads, e.g. alginate, gelatin, carbohydrates,inorganic and organic salts.

A layer of the paste 30 is deposited onto a mandrel 32 having a diameterabout equal to a desired internal diameter of a resulting graft. Theinternal diameter of the graft is preferably between 1 mm and 20 mm,more preferably in the range of 2 to 6 mm for small diameter vesselreplacement. The paste 30 is pressed onto the mandrel 32 with a roller34. An extractable fiber 36 is wound onto the paste layer. Theextractable fiber 36 is made of alginate, gelatin, carbohydrates,inorganic or organic salts, for example. Additionally, a non-extractablefiber, as described in the fiber winding and extraction technique, canbe wound onto the mandrel for reinforcement. Additional layers of thepaste 30 alternating with additional layers of the wound extractablefiber 36, with or without a reinforcing fiber, are deposited onto themandrel 32 until a desired graft thickness is achieved. The thickness ofthe paste 30 can vary from 0.1 to 5 mm, more preferably from 0.4 to 1.5mm, depending on the diameter of the graft. The graft can be made withas few as two layers of the paste 30, with one layer of the woundextractable fiber 36 between the two paste layers.

Progressive stages of the mandrel 32 as the method is carried out areshown in FIGS. 3 a-3 f FIG. 3 a shows a first layer of paste 38 rolledonto the mandrel 32. In FIG. 3 b, a first fiber 40 is wound onto thefirst layer of paste 38. FIG. 3 c shows a second layer of paste 42covering the first layer of paste 38 and the first fiber 40. In FIG. 3d, a second fiber 44 is wound onto the second layer of paste 42. FIG. 3e shows a third layer of paste 46 covering the first two layers of paste38 and 42 and the first two wound fibers 40 and 44. In FIG. 3 f, a thirdfiber 48 is wound onto the third layer of paste 46.

The graft material solution is then precipitated by phase precipitation,wherein the graft is immersed into a precipitation solvent, and/or bydrying. Examples of suitable precipitation solvents include water,ethanol, acetone, or combinations of any of these. The extractable fiber36 and extractable filler are extracted, either simultaneously orconsecutively, by applying a fiber extraction solvent to producechannels in the space occupied by the extractable fiber 36. A fillerextraction solvent can be the same solvent as the fiber extractionsolvent, and may vary only in temperature, e.g. a cold water fillerextraction solvent and a warm water fiber extraction solvent. Theprecipitation and extraction can be effected either simultaneously orconsecutively.

A further method for producing the graft of the invention is a particleand fiber extraction technique using a continuous method. Like thelayered method, described above, the continuous method entails preparinga paste 30 from a graft material solution and an extractable filler, andlayering the paste 30 and an extractable fiber 36 onto a mandrel 32, asshown in FIG. 2. However, in this method, the paste 30 is deposited ontothe mandrel 32 simultaneously while the extractable fiber 36, with orwithout a reinforcing, non-extractable fiber, is wound onto the mandrel32. As in the layered method, the graft material solution is thenprecipitated and the extractable fiber 36 and extractable filler areextracted, either simultaneously or consecutively.

The above-described methods can also be used to produce other items,such as a biosynthetic, whole-root aortic valve prosthesis.

While the embodiments of the invention described herein are presentlypreferred, various modifications and improvements can be made withoutdeparting from the spirit and scope of the invention. The scope of theinvention is indicated by the appended claims, and all changes that fallwithin the meaning and range of equivalents are intended to be embracedtherein.

1. A method of making a prosthesis comprising the steps of: extruding amolten polymer, wherein the polymer comprises chopped strands of solublefibers; extracting the soluble fibers with an extraction solvent; andthereafter treating the polymer to effect an open-cell structure havinghelically oriented interconnected ingrowth channels.
 2. The method ofclaim 1 wherein a blowing agent is used to extrude the molten polymer.3. The method of claim 2 wherein the blowing agent comprises a physicalblowing agent.
 4. The method of claim 2 wherein the blowing agentcomprises a chemical blowing agent.
 5. The method of claim 2 wherein theblowing agent comprises physical and chemical blowing agents.
 6. Themethod of claim 1 wherein the polymer comprises a polyurethane.
 7. Themethod of claim 1 wherein the polymer further comprises reinforcingfibers that are not extractable by the extraction solvent.
 8. An aorticvalve prosthesis made according to the method of claim
 1. 9. A vasculargraft prosthesis made according to the method of claim
 1. 10. The methodof claim 1, wherein the treating step is selected from the groupconsisting of heat treatment, mechanical crushing, infiltratingexplosive gas into the cells and igniting the gas, subjecting theextruded polymer to hydrolysis, and combinations thereof.